Zanidatamab Plus Chemotherapy Extends OS in First-Line HER2+ Advanced GEA

Zanidatamab-hrii (Ziihera) plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with trastuzumab (Herceptin) plus chemotherapy as first-line treatment for adults with HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), according to the second interim results from the phase 3 HERIZON-GEA-01 trial (NCT05152147) announced in a news release from the developer, Jazz Pharmaceuticals.¹ The HR for OS for zanidatamab plus tislelizumab (Tevimbra) and chemotherapy also improved with longer follow-up compared with the first interim analysis.

What were the updated overall survival results from HERIZON-GEA-01?

The zanidatamab plus chemotherapy arm demonstrated a statistically significant and clinically meaningful OS improvement compared with trastuzumab plus chemotherapy, with the HR improving relative to the first interim analysis. With longer follow-up, the HR for OS for zanidatamab plus tislelizumab and chemotherapy also improved compared with the first interim analysis, building on previously reported findings that were published in The New England Journal of Medicine.²

“Advanced [HER2-positive] GEA remains an aggressive cancer with a poor prognosis, and trastuzumab plus chemotherapy has anchored first-line treatment for years,” stated Kohei Shitara, MD, director of the department of gastrointestinal oncology and principal trial investigator at National Cancer Center Hospital East in Kashiwa, Japan, in the press release.¹ “These HERIZON-GEA-01 results show that [zanidatamab]-based regimens extend OS, demonstrating definitive superiority of [zanidatamab] over trastuzumab and setting a new benchmark for what a first-line HER2-targeted therapy can achieve.”

What safety data were reported with longer follow-up?

The safety profile of zanidatamab in combination with chemotherapy was generally consistent with the known safety profiles of the individual agents and with previously reported HERIZON-GEA-01 data. No new safety signals were observed with the extended follow-up, according to the release.

How does this update relate to the recent FDA approval of zanidatamab?

On August 25, 2026, the FDA approved zanidatamab in combination with tislelizumab and fluoropyrimidine-, and platinum-containing chemotherapy for the first-line treatment of adults with HER2-positive unresectable, locally advanced, or metastatic gastric cancers, as well as zanidatamab in combination with fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2-positive disease in the same setting.³ That was supported by the first interim HERIZON-GEA-01 data showing a median OS of 26.4 months with zanidatamab, tislelizumab, and chemotherapy vs 19.2 months with trastuzumab plus chemotherapy.

“Following the recent FDA approval, and further supported by these updated results, we are moving quickly to establish [zanidatamab] as the HER2-targeted, first-line therapy of choice, with [zanidatamab] plus tislelizumab and chemotherapy as the new standard of care in the US,” stated Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, in the press release.¹

Jazz Pharmaceuticals has submitted the updated OS data for presentation at a major medical meeting in the fourth quarter of 2026 and plans to submit the findings to global health authorities.

How was the HERIZON-GEA-01 trial designed?

HERIZON-GEA-01 is a global, randomized, open-label phase 3 trial conducted jointly with BeOne Medicines that enrolled 914 patients across approximately 225 sites in more than 30 countries. Patients with unresectable, locally advanced, recurrent, or metastatic GEA, with HER2-positive status, defined as 3+ HER2 expression by immunohistochemistry (IHC) or 2+ HER2 expression by IHC with in situ hybridization positivity per central assessment, were randomly assigned to 1 of 3 arms. They received zanidatamab plus chemotherapy and tislelizumab, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. The trial evaluated the dual primary end points of progression-free survival by blinded independent central review and OS.

References

1. Ziihera® (zanidatamab-hrii) plus chemotherapy demonstrates statistically significant overall survival benefit versus trastuzumab plus chemotherapy in first-line HER2+ advanced GEA. News release. Jazz Pharmaceuticals plc. August 31, 2026. Accessed September 2, 2026. https://tinyurl.com/56c5tycv
2. Shitara K, Elimova E, Liu T, et al. Zanidatamab with and without tislelizumab in HER2-positive gastroesophageal cancer. N Engl J Med. 2026;394(20):2002-2014. doi:10.1056/NEJMoa2517729
3. U.S. FDA approves Ziihera® (zanidatamab-hrii) with and without tislelizumab plus chemotherapy in first-line HER2+ advanced gastroesophageal adenocarcinoma. News release. Jazz Pharmaceuticals plc. August 25, 2026. Accessed September 2, 2026. https://tinyurl.com/4d7s97mm